Synergistic Oxidative Damage with Gene Therapy Potentiates Targeted Sterilization of Broad-Spectrum Microorganisms

Nanoparticle-based approaches addressed the barriers to antibiotic resistance faced by traditional antimicrobial agents. However, nanotherapies against multibacterial infections still suffered from the lack of broad-spectrum targeting ability and the mono-inhibition pathway. In this study, a multimodality therapeutic nanoplatform (denoted as Asza) is introduced, which combines specific recognition, synergistic oxidative damage, and gene therapy, to effectively inhibit the emergence of bacterial resistance, achieving broad-spectrum sterilization activity against two Gram-positive (B. subt, S. epider) and two Gram-negative bacteria (E. coli, E. aero). In addition to the oxidative damage generated from gold nanoclusters, DNA aptamer, and CRISPR-Cas modules are combined in the Asza to recognize multiple bacteria and cleave the ftsz gene with high specificity, allowing precision treatment of multibacterial infections without damaging surrounding healthy cells. Furthermore, multimodal antimicrobial strategies can reduce the risk of the generation of bacterial resistance to single-modality therapy and significantly boost the efficiency of antibacterial therapy. This study offers a promising approach to advance the applications of nanomaterials in clinical antimicrobial therapy.